1H MRS identifies lactate rise in the striatum of MPTP-treated C57BL/6 mice
1H MRS identifies lactate rise in the striatum of MPTP-treated C57BL/6 mice
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DOI：
10.1111/j.1460-9568.2006.04610.x
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发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
Nakai, M
中科院分区：
文献类型：
--
作者：
Koga, K;Mori, A;Nakai, M
在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）处理的帕金森病（PD）实验模型中，线粒体功能障碍与黑质纹状体多巴胺能神经元的死亡有关。在这里，我们利用质子磁共振波谱（H-1 MRS），以确定在纹状体的MPTP治疗的C57 BL/6小鼠的能量代谢的变化。乳酸/肌酸（Lac/Cr）比值显着增加，观察到在2小时，然后迅速恢复到约7小时后注射MPTP的基础水平。神经化学和蛋白质印迹分析表明，多巴胺含量和蛋白质水平的酪氨酸羟化酶和多巴胺转运蛋白在纹状体深刻的MPTP治疗后3天下降。预处理与deprenyl，单胺氧化酶B抑制剂，或GBR-12909，多巴胺摄取抑制剂，几乎完全衰减的纹状体Lac/Cr比的增加和随后的损失的多巴胺能神经末梢MPTP处理的小鼠。本研究表明，H-1 MRS是一个敏感的措施，在PD小鼠模型的脑生化改变，并进一步表明，在纹状体Lac/Cr比值的增加，由MPTP诱导可能与线粒体能量危机，其次是多巴胺能神经毒性。
Mitochondrial dysfunction has been implicated in the death of nigrostriatal dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated experimental models of Parkinson's disease (PD). Here we utilized proton magnetic resonance spectroscopy (H-1 MRS) to identify changes in energy metabolism in the striatum of MPTP-treated C57BL/6 mice. Remarkable increases in lactate/creatine (Lac/Cr) ratio were observed at 2 h and then quickly returned to about the basal level by 7 h after injection of MPTP. Neurochemical and Western blot analyses revealed that dopamine contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased at 3 days after MPTP treatment. Pretreatment with deprenyl, a monoamine oxidase B inhibitor, or GBR-12909, a dopamine uptake inhibitor, almost completely attenuated both the increases in striatal Lac/Cr ratio and the subsequent loss of dopaminergic nerve terminals in MPTP-treated mice. The present study indicates that H-1 MRS is a sensitive measure of biochemical alterations of the brain in a mouse model of PD, and further shows that the increases in striatal Lac/Cr ratio induced by MPTP may be associated with mitochondrial energy crisis, followed by dopaminergic neurotoxicity.